From the Guidelines
Glucocorticoid-induced leukocytosis occurs primarily through the demargination of neutrophils from the vascular endothelium, delay of neutrophil apoptosis, stimulation of neutrophil production in the bone marrow, and inhibition of neutrophil migration into tissues. The mechanism of action for leukocytosis secondary to steroid (glucocorticoid) therapy is multifaceted, involving several key processes that ultimately lead to an increase in circulating white blood cells, particularly neutrophils.
Key Mechanisms:
- Demargination of neutrophils: Steroids cause neutrophils to shift from the marginated pool into circulation, rapidly increasing their numbers in the bloodstream 1.
- Delayed neutrophil apoptosis: Glucocorticoids extend the lifespan of neutrophils by delaying their apoptosis, which contributes to the elevated white blood cell count 1.
- Stimulation of neutrophil production: Glucocorticoids stimulate the bone marrow to increase neutrophil production and accelerate the release of mature neutrophils into circulation.
- Inhibition of neutrophil migration: Steroids inhibit the migration of neutrophils out of blood vessels into tissues, keeping more cells in the bloodstream. This effect is dose-dependent, temporary, and resolves when the medication is discontinued. It is essential to recognize this phenomenon as a normal physiological response to steroids rather than a sign of infection, although other causes of leukocytosis should still be considered when evaluating patients on steroid therapy.
From the Research
Mechanism of Action for Leukocytosis Secondary to Steroids
The mechanism of action for leukocytosis secondary to steroid (glucocorticoid) therapy involves several key processes:
- Decreased margination of neutrophils, which reduces their adhesion to the endothelial lining of blood vessels, allowing more neutrophils to circulate in the bloodstream 2, 3
- Increased release of neutrophils from the bone marrow, which is thought to be mediated by the induction of granulocyte-colony stimulating factor (G-CSF) 2, 3
- Down-modulation of neutrophil L-selectin and Mac-1 expression, which reduces the ability of neutrophils to adhere to the endothelium and migrate out of the bloodstream 2
Key Factors Involved
Some key factors involved in the mechanism of action for leukocytosis secondary to steroids include:
- Granulocyte-colony stimulating factor (G-CSF), which is induced by glucocorticoids and promotes the production and release of neutrophils from the bone marrow 2, 3
- L-selectin and Mac-1, which are adhesion molecules expressed on the surface of neutrophils and play a role in their migration and adhesion to the endothelium 2
- Endothelial-leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1), which are expressed on the surface of endothelial cells and play a role in the adhesion and migration of neutrophils 4
Effects on Neutrophil Function
Glucocorticoids do not appear to functionally inactivate neutrophils, but rather inhibit their accumulation at inflammatory sites by reducing the production of chemoattractants and endothelial activators 5
- Neutrophil degranulation, chemotaxis, and binding to vascular endothelium are not significantly affected by glucocorticoids 5
- Glucocorticoids may inhibit the spontaneous adherence of neutrophils to endothelial cells, but do not affect their binding to endothelial cells stimulated by leukocyte activators or endothelial activators 5